Since the first documented outbreaks in 1982, infections from enterohemorrhagic Escherichia coli (SHEC), now more commonly referred to as Shiga toxin producing E. coli (STEC), have been a major public health concern in the United States and in Europe. It is recognized that the Shiga and Shiga like toxins of Escherichia coli 0157:H7 and of other Shiga-producing E. Coli strains are pathogenesis factors. In the United States, an estimated 73,000 cases of E. coli 0157:H7 and 37,000 non-0157 cases occur annually. Most of the cases occur in children less than 5 years of age. The risk of developing hemolytic uremic syndrome (HUS) following EHEC infection is 3-26%. Usually 5-10% of patients with overt STEC disease develop HUS. There is strong evidence that all postdiarrheal HUS is caused by STEC. HUS is recognized as the major cause of kidney failure in infants and children worldwide. About one-third of HUS patients have abnormal kidney function for many years. About 8% have life long complications such as high blood pressure, seizures, blindness, paralysis . . . (Ostroff, Kobayashi et al. 1989). A small percentage, 0.1-2%, die. Of those who survive HUS, one study showed that half had persistend kidney disease, and 18% progress to end stage renal failure. Mortality in the US from HUS has been estimated to consist of 61 persons. There is no available treatment and antibiotics and anti-diarrheals may exacerbate the problem. Outbreaks of disease have been reported in association with consumption of hamburgers in fast food chains, in nursing homes and in day-care centers. While consumption of contaminated meats, fruits, vegetable and water have led to outbreaks, person to person contact is now recognized as a key mode of transmission (Spika, Parsons et al. 1986). Although STEC infection occurs mainly in children, adults are also susceptible. Worldwide incidence of STEC infection and HUS appears to be similar to that found in the U.S. Since 1996 STEC infection is notifiable in most states. The disease peaks in the warm months but may occur at any time of the year. Bloody diarrhea usually occurs prior to systemic complications which can be either fatal, due to acute renal failure and serious neurological involvement, or lead to permanent kidney damage. The kidney damage and the neurological symptoms which are caused by one of 2 toxins is known as hemolytic uremic syndrome (HUS). In children there is normally a prodromal period of 4 to 7 days between the bloody diarrhea and development of HUS. During this prodromal period an effective preventative treatment, if one was a vailable, might prevent the development of HUS.
Currently there are three accepted characteristics of all STEC strains. First, they all harbor lysogenic lambdoid phages that encode the Shiga toxins. Prophage induction is likely required for toxin production. Shiga and Shiga-like toxins were previously referred to as verotoxins due to their toxicity to vero cells. Shiga-like toxins consist of one enzymatically active A subunit and five B subunits that are responsible for cell binding. The toxins are potent protein synthesis inhibitors and are particularly cytotoxic to both HeLa and Vero cells in culture. Based on antigenic relatedness to Shiga toxin, there are two general classes of Shiga-like toxins. Shiga-like toxin I is neutralized by antibody against Shiga toxin, the toxin produced by Shigella dysenteriae type I strains. Shiga-like toxin II is defined as toxin which is not neutralized by antibody directed against Shiga toxin. By amino acid sequence comparison, SLT-I and SLT-II are 56% homologous. The two toxins have identical sets of glycolipid receptors and an identical mode of action. All EHEC strains isolated to date have been found to produce either one toxin or both. The role of toxin in the pathogenesis of both hemorrhagic colitis and hemolytic uremic syndrome is still not definitive. However, there is strong circumstantial evidence linking SLT II with HUS.